title: Retinitis Pigmentosa: over-expression of anti-ageing protein Klotho in degenerating photoreceptors.
abstract: Retinitis Pigmentosa involves a hereditary degeneration of photoreceptors by as yet unresolved mechanisms. The secretable protein α-Klotho has a function related to ageing processes, and α-Klotho-deficient mice have reduced lifespan and declining functions in several tissues. Here, we studied Klotho in connection with inherited photoreceptor degeneration. Increased nuclear immunostaining for α-Klotho protein was seen in degenerating photoreceptors in four different Retinitis Pigmentosa models (rd1, rd2 mice; P23H, S334ter rhodopsin mutant rats). Correspondingly, in rd1 retina α-Klotho mRNA expression was significantly up-regulated. Moreover, immunostaining for another Klotho family protein, β-Klotho, also co-localized with degenerating rd1 photoreceptors. The rd1 retina displayed reduced levels of fibroblast growth factor 15, a member of the fibroblast growth factor subfamily for which Klotho acts as a co-receptor. Exogenous α-Klotho protein added to retinal explant cultures did not affect cell death in rd1 retinae, but caused a severe layer disordering in wild-type retinae. Our study suggests Klotho as a novel player in the retina, with a clear connection to photoreceptor cell death as well as with an influence on retinal organization.
authors.affiliation: Division of Ophthalmology, Department of Clinical Sciences, Lund, University of Lund, Lund, Sweden; Division of Experimental Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
authors.forename: Pietro
authors.initials: P
authors.lastname: Farinelli
authors.forename: Blanca
authors.initials: B
authors.lastname: Arango-Gonzalez
authors.forename: Jakob
authors.initials: J
authors.lastname: Völkl
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: François
authors.initials: F
authors.lastname: Paquet-Durand
authors.forename: Per A R
authors.initials: PA
authors.lastname: Ekström
mesh_terms: D000818:Animals; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism* / Q000494:pharmacology; D000090265:Klotho Proteins; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000378:metabolism* / Q000473:pathology; D046509:Tissue Culture Techniques; D015854:Up-Regulation
chemical_list: C418622:Klb protein, mouse; D008565:Membrane Proteins; D020033:Protein Isoforms; C108526:fibroblast growth factor 15, mouse; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Retinitis Pigmentosa; anti-ageing protein; growth factor; neurodegeneration